What is the recommended treatment for Duchenne muscular dystrophy?

Recommended Treatment for Duchenne Muscular Dystrophy

Glucocorticoids (prednisone 0.75 mg/kg/day or deflazacort 0.9 mg/kg/day) are the primary recommended treatment for Duchenne muscular dystrophy (DMD), initiated when patients reach a functional plateau or decline phase, typically around 6 years of age. 1

Pharmacological Management

First-Line Therapy

• Glucocorticoids:
  • Prednisone: 0.75 mg/kg/day
  • Deflazacort: 0.9 mg/kg/day
  • Maximum dose: 40 kg (prednisone 30 mg/day or deflazacort 36 mg/day) 1
  • Benefits: Retards muscle strength deterioration, reduces scoliosis risk, stabilizes pulmonary function, and potentially improves cardiac function
  • Initiation: When in functional plateau or decline phase (generally around 6 years)
  • Continue even when non-ambulatory

Targeted Therapy

• Eteplirsen (EXONDYS 51):
  • Indicated specifically for DMD patients with confirmed mutations amenable to exon 51 skipping 2
  • Administered via intravenous infusion
  • Approved under accelerated approval based on increased dystrophin in skeletal muscle
  • Most common adverse reactions: balance disorder and vomiting 2

Cardiac Management

• ACE inhibitors:
  • First-line cardiac therapy
  • Initiate at 10 years of age unless contraindicated 1
  • Angiotensin receptor blockers (ARBs) as alternative if ACE inhibitors not tolerated

Respiratory Management

• Regular pulmonary evaluation with FVC and PCF measurements
• Refer to respiratory specialist when:
  • Sleep disorder symptoms appear
  • PCF < 270 L/min
  • FVC ≤ 50% of predicted value 1
• Complete pneumococcal vaccination before initiating glucocorticoids
• Prefer inactivated vaccines over live vaccines in patients on corticosteroids 1

Rehabilitation and Monitoring

• Physical therapy and occupational therapy evaluations every 4 months
• Monitor disease progression using functional scales:
  • Vignos lower limb scale
  • North Star ambulatory assessment 1
• Routine clinical appointments every 6 months
• Cardiac function evaluation every 6-12 months 1

Surgical Management

• Consider scoliosis surgery when Cobb angle is between 30-50 degrees
• Preoperative evaluation by pulmonologist and cardiologist at least 2 months before any surgery 1

Glucocorticoid Side Effect Management

• Monitor for weight gain and cushingoid appearance (most common side effects) 3
• If side effects are unmanageable, reduce dose by 25-33% 1
• Lower doses (0.30-0.35 mg/kg/day) show lesser but similar benefits with fewer side effects 3

Important Considerations

• While exon skipping agents like eteplirsen produce a smaller dystrophin protein, they preserve significant function and slow disease progression 4
• Despite strong evidence for glucocorticoid efficacy, there is wide variation in treatment regimens used globally 5
• Alternative dosing regimens (intermittent dosing, weekend dosing) exist but have less robust evidence than daily dosing 1, 6
• Long-term benefits of glucocorticoids include prolongation of functional ability and slower progression of weakness 3, 7

Treatment Algorithm

1. Confirm DMD diagnosis
2. For patients ≥6 years in functional plateau/decline:
   • Start glucocorticoids (prednisone 0.75 mg/kg/day or deflazacort 0.9 mg/kg/day)
   • If mutation amenable to exon 51 skipping, consider eteplirsen
3. At 10 years of age: Start cardiac therapy with ACE inhibitors
4. Monitor and manage respiratory function
5. Implement regular physical and occupational therapy
6. Evaluate for surgical interventions as needed